title: NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.
abstract: Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.
authors.affiliation: Department of Medical Chemistry, Biochemistry, and Biotechnology, University of Milan, 20090 Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Anastasia
authors.forename: Nadia
authors.initials: N
authors.lastname: Papini
authors.forename: Francesca
authors.initials: F
authors.lastname: Colazzo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Palazzolo
authors.forename: Cristina
authors.initials: C
authors.lastname: Tringali
authors.forename: Loredana
authors.initials: L
authors.lastname: Dileo
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.forename: Erika
authors.initials: E
authors.lastname: Conforti
authors.forename: Clementina
authors.initials: C
authors.lastname: Sitzia
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.forename: Maurilio
authors.initials: M
authors.lastname: Sampaolesi
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.forename: Bruno
authors.initials: B
authors.lastname: Venerando
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000378:metabolism*; D020868:Gene Silencing; D006868:Hydrolysis; D051379:Mice; D008956:Models, Chemical; D018482:Muscle, Skeletal / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism
chemical_list: D005679:G(M3) Ganglioside; D013107:Sphingolipids; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C511796:Neu3 protein, mouse; D009439:Neuraminidase